Electron-spectroscopic imaging--a method for analysing the distribution of light elements in mammalian cells and tissues.

Electron-spectroscopic imaging (ESI) represents a method which is based on electron energy loss spectroscopy (EELS) and renders possible to image the spatial distribution of light and medium-weight elements, i.e. especially of biologically relevant elements. In the present study, the validity of the method for biological problems was investigated by analysing the time-dependent, subcellular distribution of titanium following treatment with the cytostatically active compound titanocene dichloride in the liver, which is known to be the organ where titanium mainly accumulates following therapy with titanocene dichloride, and in 3 xenografted human tumours which are known to be sensitive to the antitumour action of titanocene dichloride. In all cases, it was shown that titanium primarily accumulates in the nuclei of hepatocytes and tumour cells and that it is thereafter incorporated into cytoplasmic lysosomes. Interestingly, phosphorus is always enriched together with titanium. These results give remarkable hints to the cellular mode of action of titanocene dichloride and, moreover, qualify the ESI technique to be a valuable method for investigating the subcellular distribution of endogenously present or exogenously light and medium-weight element.